Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines
Abstract: Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family Flaviviridae. Candidate live-attenuated vaccine (LAV) viruses with engineered deletions in the 3? untranslated region (UTR) provide immunity and protection in animal models of ZIKV infection, and phenotyp...
| Autor principal: | Collins, Natalie D |
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| Outros Autores: | Shan, Chao, Nunes, Bruno Tardelli Diniz, Widen, Steven G, Shi, Pei-Yong, Barrett, Alan D. T, Sarathy, Vanessa V |
| Grau: | Artigo |
| Idioma: | eng |
| Publicado em: |
MDPI
2020
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| Assuntos: | |
| Acesso em linha: |
http://patua.iec.gov.br//handle/iec/4087 |
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ir-iec-4087 |
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dspace |
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ir-iec-40872020-04-29T18:45:22Z Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines Collins, Natalie D Shan, Chao Nunes, Bruno Tardelli Diniz Widen, Steven G Shi, Pei-Yong Barrett, Alan D. T Sarathy, Vanessa V Zika virus / patogenicidade Infec??o por Zika virus / virologia Vacinas / an?lise Varia??o Gen?tica Sequenciamento Completo do Genoma Abstract: Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family Flaviviridae. Candidate live-attenuated vaccine (LAV) viruses with engineered deletions in the 3? untranslated region (UTR) provide immunity and protection in animal models of ZIKV infection, and phenotypic studies show that LAVs retain protective abilities following in vitro passage. The present study investigated the genetic diversity of wild-type (WT) parent ZIKV and its candidate LAVs using next generation sequencing analysis of five sequential in vitro passages. The results show that genomic entropy of WT ZIKV steadily increases during in vitro passage, whereas that of LAVs also increased by passage number five but was variable throughout passaging. Additionally, clusters of single nucleotide variants (SNVs) were found to be present in the pre-membrane/membrane (prM), envelope (E), nonstructural protein NS1 (NS1), and other nonstructural protein genes, depending on the specific deletion, whereas in the parent WT ZIKV, they are more abundant in prM and NS1. Ultimately, both the parental WT and LAV derivatives increase in genetic diversity, with evidence of adaptation following passage. This research was funded in part by a Gillson-Longenbaugh Foundation grant to A.D.T.B. P.-Y.S. was supported in part by NIH grants AI142759, AI145617, AI127744, AI136126, and UL1TR001439, and awards from the Kleberg Foundation, John S. Dunn Foundation, Amon G. Carter Foundation, and Gillson-Longenbaugh Foundation. 2020-04-29T17:13:53Z 2020-04-29T17:13:53Z 2020 Artigo COLLINS, Natalie D. et al. Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines. Vaccines, v. 8, n. 2, p. 1-9, 2020. 2076-393X http://patua.iec.gov.br//handle/iec/4087 10.3390/vaccines8020161 eng Acesso Aberto application/pdf MDPI |
| institution |
Instituto Evandro Chagas (IEC) |
| collection |
PATUA |
| language |
eng |
| topic |
Zika virus / patogenicidade Infec??o por Zika virus / virologia Vacinas / an?lise Varia??o Gen?tica Sequenciamento Completo do Genoma |
| spellingShingle |
Zika virus / patogenicidade Infec??o por Zika virus / virologia Vacinas / an?lise Varia??o Gen?tica Sequenciamento Completo do Genoma Collins, Natalie D Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| topic_facet |
Zika virus / patogenicidade Infec??o por Zika virus / virologia Vacinas / an?lise Varia??o Gen?tica Sequenciamento Completo do Genoma |
| description |
Abstract: Zika virus (ZIKV) is a mosquito-transmitted positive-sense RNA virus in the family
Flaviviridae. Candidate live-attenuated vaccine (LAV) viruses with engineered deletions in the
3? untranslated region (UTR) provide immunity and protection in animal models of ZIKV infection,
and phenotypic studies show that LAVs retain protective abilities following in vitro passage. The
present study investigated the genetic diversity of wild-type (WT) parent ZIKV and its candidate
LAVs using next generation sequencing analysis of five sequential in vitro passages. The results show
that genomic entropy of WT ZIKV steadily increases during in vitro passage, whereas that of LAVs
also increased by passage number five but was variable throughout passaging. Additionally, clusters
of single nucleotide variants (SNVs) were found to be present in the pre-membrane/membrane (prM),
envelope (E), nonstructural protein NS1 (NS1), and other nonstructural protein genes, depending
on the specific deletion, whereas in the parent WT ZIKV, they are more abundant in prM and NS1.
Ultimately, both the parental WT and LAV derivatives increase in genetic diversity, with evidence of
adaptation following passage. |
| format |
Artigo |
| author |
Collins, Natalie D |
| author2 |
Shan, Chao Nunes, Bruno Tardelli Diniz Widen, Steven G Shi, Pei-Yong Barrett, Alan D. T Sarathy, Vanessa V |
| author2Str |
Shan, Chao Nunes, Bruno Tardelli Diniz Widen, Steven G Shi, Pei-Yong Barrett, Alan D. T Sarathy, Vanessa V |
| title |
Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| title_short |
Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| title_full |
Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| title_fullStr |
Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| title_full_unstemmed |
Using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| title_sort |
using next generation sequencing to study the genetic diversity of candidate live attenuated zika vaccines |
| publisher |
MDPI |
| publishDate |
2020 |
| url |
http://patua.iec.gov.br//handle/iec/4087 |
| _version_ |
1717584482687516672 |
| score |
11.755432 |